{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:02:49Z","timestamp":1790226169175,"version":"4.1.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Cancer of unknown primary (CUP) is primarily treated with empirical chemotherapy, but clinical outcomes remain unsatisfactory. We present the case of a 62-year-old male with asymptomatic left supraclavicular lymphadenopathy. Fine-needle aspiration revealed metastatic poorly differentiated carcinoma. Comprehensive evaluation, including contrast-enhanced computed tomography (CT), fluorodeoxyglucose positron emission tomography\/CT (FDG-PET\/CT), nasopharyngoscopy, and gastroscopy, failed to identify a definite primary tumor, leading to a diagnosis of CUP. Initial empirical chemotherapy with liposomal paclitaxel and nedaplatin showed limited efficacy and was complicated by grade 3 treatment-related adverse events (TRAEs), resulting in discontinuation due to poor tolerability. Subsequently, a core needle biopsy was performed. Immunohistochemistry suggested metastatic renal cell carcinoma (RCC). A 90-gene expression assay identified the kidney as the most likely primary site, with a similarity score of 82.6. The regimen was then switched to site-specific therapy with lenvatinib plus camrelizumab. The patient tolerated treatment well, experiencing only grade 1 TRAEs. Follow-up contrast-enhanced CT scans demonstrated significant lesion regression (33.1% and 69.6% reductions at 2 and 4 months, respectively), achieving a best response of partial response (PR). In conclusion, the combination of lenvatinib and camrelizumab demonstrated a favorable short-term response and acceptable tolerability in this patient, and renal-like CUP represents a distinct favorable CUP subset.<\/jats:p>","DOI":"10.3389\/fonc.2026.1883469","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:39:03Z","timestamp":1790224743000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Site-specific therapy guided by the 90-gene expression assay in cancer of unknown primary: lenvatinib plus camrelizumab for occult renal cell carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Liangshan","family":"Da","sequence":"first","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Da","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanren","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2402691","article-title":"Cancer of unknown primary site","volume":"392","author":"Raghav","year":"2025","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO-25-02189","article-title":"Is it time to retire the unified cancer of unknown primary concept in the precision oncology era","volume":"44","author":"Subbiah","year":"2026","journal-title":"J Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-025-01060-8","article-title":"Rethinking cancer of unknown primary: from diagnostic challenge to targeted treatment","volume":"22","author":"Pouyiourou","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70161","article-title":"Advancements in diagnostics and therapeutics for cancer of unknown primary in the era of precision medicine","volume":"6","author":"Zhao","year":"2025","journal-title":"MedComm (2020)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt099","article-title":"Molecular profiling diagnosis in unknown primary cancer: accuracy and ability to complement standard pathology","volume":"105","author":"Greco","year":"2013","journal-title":"J Natl Cancer Inst"},{"key":"B6","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s00428-014-1545-2","article-title":"Gene expression profiling in patients with carcinoma of unknown primary site: from translational research to standard of care","volume":"464","author":"Hainsworth","year":"2014","journal-title":"Virchows Arch"},{"key":"B7","doi-asserted-by":"publisher","first-page":"5686","DOI":"10.1038\/s41467-023-41015-0","article-title":"DNA methylation profiling to determine the primary sites of metastatic cancers using formalin-fixed paraffin-embedded tissues","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat Commun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00533","article-title":"The quest for improving treatment of cancer of unknown primary (CUP) through molecularly-driven treatments: a systematic review","volume":"10","author":"Lombardo","year":"2020","journal-title":"Front Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02915-w","article-title":"Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning","volume":"30","author":"Tian","year":"2024","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s12967-022-03318-6","article-title":"Clinical validation of a 90-gene expression test for tumor tissue of origin diagnosis: a large-scale multicenter study of 1417 patients","volume":"20","author":"Sun","year":"2022","journal-title":"J Transl Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1159\/000551434","article-title":"(Un-)known chances: emerging hope for cancer of unknown primary - 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